Pliable medical device and method of use

ABSTRACT

A firm but pliable medical device for use as a bone graft substitute or bone graft extender retains its shape without the requirement of a containment device, such as a syringe. Because the device is solid, it is easy to locate or position in-vivo and, in the moist environment of the body, it will hold its shape well, for an extended time. Because the lyophilized pliable medical device is porous, it adsorbs blood and other beneficial cells containing body fluids, such as bone marrow, contributing to its superior bone repair efficacy in comparison to an analogous putty that has not been lyophilized. In addition these lyophilized pliable medical devices are easier to terminally steam sterilize than the analogous putty because there is no moisture present to boil and “blow-out” of the containment device (syringe). The glycerin that is present in the formulation lends pliability but has a low vapor pressure.

FIELD OF THE INVENTION

This invention relates to the field of surgical repair of skeletalelements. More particularly, the invention is a method and compositionfor use as a bone graft substitute or bone graft extender for filling orotherwise repairing bone damage and promoting bone formation in mammalsusing a composition that is a firm but pliable medical device that willretain its shape without the requirement of a containment device, suchas a syringe.

BACKGROUND OF THE INVENTION

Physicians are sometimes called upon to repair bone that has beendamaged by disease, trauma, osseous surgery or other causes, or to causebone material to grow where there has been no bone before, such asduring a spine fusion procedure. As an outcome of that procedure, it isdesirable for two or more vertebral bodies to be maintained in aspecific orientation. This can be accomplished by growing a column orbridge of rigid bone between the vertebral bodies. This maintains themin a fixed position relative to each other. The repair of long bonefractures can often be accomplished merely by relocating disrupted boneelements into natural proximity and fixing them in place until they canheal together. This is the approach taken in repairing ordinary limbfractures, for example. The fractured bone is re-set, then immobilizedfor a period of weeks in a rigid or semi-rigid cast or splint as thefractured elements heal.

Sometimes, however, this approach is insufficient because the patienthas lost some of the bone. This can happen in certain kinds of traumawhere the bone is so badly shattered that it cannot feasibly be piecedtogether. More often, it happens as a result of disease that destroysbone mass or as the result of osseous surgery in which destruction ofbone mass is unavoidable. In these cases, there is no “piece” of thepatient's bone to re-set into proper position for healing. Instead,there is a void or defect that must somehow be filled, or a gap betweentwo bone structures that needs to be filled with new bone. The fillingof this defect or gap requires a material that is not only biocompatiblebut preferably will accept or even promote in-growing natural bone asthe site heals. In such a manner, the material ideally will eventuallybecome resorbed as new in-growing natural bone takes its place as partof the skeletal structure. Completely resorbed material eliminates thepossibility for a stress riser that can occur when foreign matterremains in the skeleton, potentially giving rise to a fracture in thefuture.

Numerous bone replacement materials have been employed by physicianswith varying degrees of success. One approach is to use bone materialrecovered from the patient himself, or so-called autologous bone. Thisapproach is advantageous in that it avoids biocompatibility andbio-rejection problems. However, such an approach necessarily involvestwo surgical procedures, two surgical sites, and two healingprocesses-one for the original injury and a second for the site of thedonated bone material. This means greater cost, and increased risk ofinfection and morbidity for a patient that is already seriously ill orinjured. Also, this approach can require a great deal of time andsurgical skill as the surgeon removes the donated material from thedonation site, shapes and fits it to the primary site, and then repairsboth sites. Finally, there is quite obviously a limit to the amount ofbone in the patient's body available to be sacrificed as donor material.

Another approach uses human bone but not harvested from the patient.This is called allograft bone. Allograft bone is typically harvestedfrom cadavers. It contains endogenous bone morphogenic proteins (“BMP”)and is available both in structurally intact and demineralized forms.Such material can become integrally incorporated into the patient's ownskeletal system.

Demineralized allograft is routinely offered by commercial medicalsuppliers in dry granulated or powdered form of varying fineness. Thesedry granules or powder generally lack sufficient cohesiveness andadhesion for filling an osseous defect. Therefore, they are mixed withan appropriate carrier. The carrier in the past has sometimes been thepatient's own blood or bone marrow. Such a carrier is of courseplentiful at the surgical site, is biocompatible with the patient, andcontains biological agents that promote new growth in the allograft boneelements suspended in it. On the other hand, using the patient's ownblood necessitates a mixing step which might not be controlled preciselyin the operating room to achieve the desired consistency. In addition,blood is not of the ideal consistency or viscosity for such anapplication.

Glycerol and other biocompatible materials have been used as alternatecarriers in combination with demineralized allograft bone. Glycerol issuitable in consistency and viscosity for this application, but suffersfrom certain functional drawbacks. Because glycerol is water soluble, itcould allow early dispersement of the suspended bone after being placedin the bone defect at the injury site.

Purified forms of human or animal derived collagen have been describedpreviously for use in bone graft substitutes. When used by itself, inlyophilized form, collagen is not entirely suitable for use as a bonegraft substitute. It resorbs too quickly to be an effective scaffold forbone accretion. In order for bone formation to occur, osteogenic cells(cells capable of producing bone) must attach to the osteoconductivesubstrate and begin the process of bone formation. The substrate mustremain present long enough to allow bone formation to progress to thepoint of being self sustaining. Collagen can be chemically modified tomake it less bioresorbable. Chemical cross linking agents such asformaldehyde and glutaraldehyde have been described. Unfortunately, lowresidual levels of these agents are cytotoxic and can affect boneformation in a negative manner.

Lyophilized collagen devices also compress, under soft tissue forces,not maintaining an adequate space for bone ingrowth to occur. In suchcircumstances, collagen can be used in combination with alloplastmaterials for maintaining an adequate “healing volume.” Even in theseinstances though, collagen still suffers the disadvantage of being apossible sensitizing agent in patients at risk for having an allergicresponse to collagen. In the case of bovine or other animal collagen,there is also a concern about the transmission of animal diseases, suchas Bovine Spongiform Encephalopathy (BSE, or Mad Cow Disease) to thepatient.

As a substitute for glycerol, high-molecular weight hydrogels, such assodium hyaluronate, have been used to form a malleable bone putty whichincludes allograft bone powder suspended therein. Hyaluronon is apolysaccharide that occurs naturally in the body in the form ofhyaluronic acid or in the salt form such as sodium hyaluronate. It ishighly hydrophilic, viscous, and extremely lubricous. High-molecularweight hydrogels will allow suspension of very small particle sizes ofallograft material.

However, even hydrogels may tend to disperse from the bone defect site.In addition, hydrogels are not conducive to retaining the body's ownfluids or bone marrow aspirate which may be delivered to the defectsite. There is therefore a need in the art for an improved bone graftsubstitute that overcomes these and other deficiencies.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a picture of a cylinder shaped embodiment of the pliablemedical device of the present invention and its flexibility.

FIG. 2 shows a picture of a cylinder shaped embodiment of the pliablemedical device of the present invention being cut with scissors.

FIG. 3 shows a picture of a cylinder shaped embodiment of the pliablemedical device of the present invention being placed into a bone defect.

FIG. 4 shows a picture of a sheet embodiment of the pliable medicaldevice of the present invention and its flexibility.

FIG. 5 shows a picture of a cube shaped embodiment of the pliablemedical device of the present invention being placed into a metal spinefusion cage.

FIG. 6 shows a picture of a cube shaped embodiment of the pliablemedical device of the present invention being placed into a hollowcentral portion of a fibular ring allograft device.

DETAILED DESCRIPTION OF THE INVENTION

The nature of the present invention begins with the preparation of ahydrogel material. The following description is by way of example, andspecific amounts of material listed may be varied substantially toachieve the same or similar results. Thus, the specific amounts shownbelow are by way of example only and are not intended to be limiting tothe scope of the invention.

A mixing operation is performed in a stainless steel, one quart, Rossdouble planetary mixing unit fitted with a closure allowing foroperation under partial vacuum. First, 31.5 grams of sodiumcarboxymethylcellulose (NaCMC) is completely dispersed in 145.3 grams ofglycerin (USP). The dispersion is added in approximately equal amountsto each of three 60 ml disposable plastic Luer-lock fitted syringes.Alternatives to glycerin are possible, such as polyethylene glycols,N-methyl pyrrolidone, and triacetin.

With the mixing unit under partial vacuum (15 inches of mercury (Hg))one of the NaCMC dispersion containing syringes is connected to themixing unit via a Luer-lock fitted entry port and the contents of thesyringe are added to the mixing unit. While mixing at a moderate speed(100 rpm) about 30% of a total of 823.2 grams of sterile water forinjection (WFI) is added to the mixing unit. Next, the contents of asecond NaCMC dispersion containing syringe is added to the mixing unitalong with an additional 30% of the total WFI. Finally, contents fromthe third NaCMC dispersion containing syringe and all but about fifty mlof the remaining WFI is added to the mixing unit. The remainder of theWFI is used to rinse the syringe entry port. The vacuum in the mixingunit is adjusted to greater than twenty inches of Hg and the contentsmixed at medium speed (150 rpm) for about thirty-five minutes. Then, thevacuum is broken and mixing discontinued. The resulting hydrogelmaterial from the mixing unit is transferred to a closed storagecontainer. The hydrogel material is allowed to hydrate at roomtemperature, about 25° C. for at least six hours. The process may bespeeded up by placing the closed storage container in an environmentwith an elevated temperature, such as 40° C.

Next, about 240 grams of the hydrated hydrogel material is transferredto the mixing unit along with about 130 grams of anorganic bone mineralmatrix (ABM), a calcium phosphate ceramic, which may be coated with abiologically active peptide. Several different biologically activepeptides may be used. For example, P-15 is a peptide fragment taken fromType I collagen and acts as a cell binding agent. Chrysalin is a peptidefragment taken from the biomolecule thrombin. Chrysalin is reported tohave effects on blood vessel formation. Cytomodulin is a bioactive 7amino acid synthetic protein patterned after a peptide sequence found inthe biomolecule TGF-beta. Cytomodulin is further described in U.S. Pat.No. 5,661,127. The alpha1(I)-CB3 fragment of type I collagen containsthe reportedly biologically active fragment DGEA [J. Biol. Chem, 266(12)p-7363 (1991)] that bind the alpha2/beta1 integrin. Type I collagen alsocontains the well know RGD peptide sequence that acts as a fibronectinreceptor. There are well known peptide fragments of the parathyroidhormone, e.g., the 1-34 PTH fragment, that have biological activity onthe skeleton. Other examples of biologically active synthetic peptidefragments based on sequences from the biomolecules Angiotensin I and IIare described in U.S. Pat. No. 6,916,783. These biologically activepeptides may also be used in these pliable medical devices.

ABM is the “osteoconductive component” of the pliable medical device. Anosteoconductive material is one that promotes bone deposition, providedthat fully differentiated and competent osteogenic cells are availableat the site of implantation. In addition to anorganic bone mineralmatrix (ABM), the osteoconductive component may also be a syntheticalloplast matrix or some other type of xenograft or allograftmineralized matrix that might not fit the definition of “anorganic.” Thealloplast could be a calcium phosphate material or it could be one ofseveral other inorganic materials that have been used previously in bonegraft substitute formulations, e.g., calcium carbonates, calciumsulphates, calcium silicates, or mixtures thereof that could function asbiocompatible, osteoconductive matrices. The anorganic bone mineralmatrix, synthetic alloplast matrix, and xenograft or allograftmineralized matrix are collectively referred to as the osteoconductivecomponent.

The P-15 material mentioned previously is structurally identical to afifteen amino acid sequence that is found in natural Type I collagen,but is made synthetically. The P-15 used is not osteoinductive (havingthe ability to induce de novo differentiation of competent osteogeniccells from nonosteogenic and uncommitted cells). The P-15 will not takenon-bone cells and make bone cells out of them, but instead, P-15 isable to recruit cells that are already destined to become bone cells(osteogenic) and cause them to lay down on the surface of the matrix andstart making bone. This is advantageous in the event that the pliablemedical device migrates away from the osteogenic site, i.e., a sitepredisposed to growing bone cells. In such an event, no bone cells willgrow at the site of migration, whereas, an osteoinductive material,typical of the prior art products, could cause ectopic bone to growwherever the material happened to migrate, which could be verydetrimental and problematic for the patient. The pliable medical deviceneeds to be in physical contact with an osteogenic site in order forbone to grow. Thus, in a spine fusion application, a cylinder of thepliable medical device positioned at each end, adjacent to differentvertebra, will allow bone to grow from each end, and meet in the middle,forming a new bone structure that was not there before.

The P-15 coated ABM particles have a mean particle diameter of 300microns, and nearly all will fall within a range between 250 microns to425 microns. However, a particle size range between 50 microns to 2000microns may also be used. The two materials, ABM and the hydratedhydrogel material, are mixed at low speed (approximately fifty rpm) forabout two minutes. Next, a second 130 gram amount of ABM/P-15 particlesare added and mixed for an additional seventeen minutes. A vacuum of atleast twenty inches of Hg is drawn on the mixing unit and mixed for anadditional five minutes. The resulting ABM/P-15/CMC hydrogel material,hereinafter referred to as “putty”, is transferred from the mixing unitand may be stored, or processed further according to the followingsteps.

Though the putty can be used by a physician in this form to treat bonedamage, it may be further processed by a lyophilization step intoseveral different shapes. The following examples are simply illustrativeand not intended to be limiting to only the shapes described. Inaddition to the cylinder, cube, and sheet shapes described below, anyother shapes for a particular purpose could be made, such as starshaped, toroid shaped, pyramid shaped, sphere shaped, and any number ofirregularly shaped embodiments.

EXAMPLE 1 Preparation of Lyophilized Cylinders

An extrusion device is fitted with a 6.5 mm diameter orifice and filledwith the putty prepared as described above. Cylinders, fifty mm inlength, are extruded from the device onto a chilled (−30° C.) metalplate, or any other appropriate chilled surface. The cylinders arefurther cooled to −55° C. on the shelves of a lyophilization vessel.Lyophilization is a means of water removal, achieved by freezing a wetsubstance and causing the ice to sublime directly to vapor by exposingit to a surrounding low pressure. A vacuum of 200 mTorr is applied tothe frozen cylinders and maintained for eighteen hours. During that timethe lyophilization chamber is allowed to warm to room temperature,approximately 25° C., or heated somewhat to speed up the sublimationprocess. These conditions are sufficient to reduce the water content ofthe cylinders to about 3%. The resulting lyophilized cylinders are dryin appearance, flexible and able to absorb blood and serous fluids.Please see FIGS. 1-3.

Lyophilization has many advantages over simply air drying or vacuumdrying the putty. When the putty is allowed to air dry or vacuum drywithout freezing, the hydrogel forms a skin around the ABM particlesthat is occlusive and prevents cells from getting to the particles.Freezing the material first, and then evaporating the water leaves manyholes where the ice crystals sublime giving rise to a very porousstructure. The porous structure allows cells, blood, and bone marroweasy access through the holes to the particles. With air drying andvacuum drying without freezing, the hydogel structure continues tocollapse as the water evaporates, thus preventing the creation of aporous structure. Sublimation, rather than evaporation, is the key tocreating the porous structure desired.

Next, the lyophilized cylinders are placed into sealed but breathablemicrobial barrier pouches and sterilized in a steam autoclave. Thepouches may be made of paper or more typically Tyvec® from DuPont. Thesterilization cycle includes a twenty minute temperature ramp-up to 121°C., temperature maintenance at 121° C. for thirty minutes, followed by aone hour cool down period to room temperature, approximately 25° C. Thelyophilized cylinders are substantially unchanged in their physicalhandling properties following this sterilization procedure.

Because the lyophilized cylinders are easily cut into smaller pieces asshown in FIG. 2, it is easy to load those pieces directly into aosteogenic site, such as the bone defect shown in FIG. 3, or into metalspine fusion cages, such as the BAK-C cage shown in FIG. 5. This loadingcan be done before the cage is placed into the prepared inter-bodylocation during an anterior cervical spine discectomy and vertebral bodyfusion.

EXAMPLE 2 Preparation of Lyophilized Sheets

The putty prepared as described above is loaded by injection into aDelrin mold containing a channel, twenty-four mm wide by four mm deep by150 mm in length. The sheet-like mold is fitted with a releasable topplate that is typically bolted to the bottom plate. The loadedsheet-like mold is placed into a freezing unit and the sheet-like moldand putty are cooled to −55° C. After reaching this desired temperature,the top plate of the sheet-like mold is loosened to allow water tosublime away, and the sheet-like mold, still cold, is placed into alyophilization chamber at 135 mTorr. During the sublimation process thelyophilization chamber is allowed to gradually warm to room temperature,approximately 25° C., or heated somewhat to speed up the sublimationprocess. The resulting dry flexible lyophilized sheet is easily removedfrom the mold and cut with standard scissors (FIG. 4). The lyophilizedsheet is compliant for fitting onto an irregular surface. When dampened,the sheet maintains its proximity to the applied surface very well. Thelyophilized sheet could also be sterilized in a steam autoclave asdescribed above, prior to use.

High energy tibial fractures (auto accidents) are prone to becomingnon-unions. These non-unions are often repaired by debrieding the softtissue from the non-union area and loading the open space between thefracture ends with autograft bone. To better localize the autograftbone, a lyophilized sheet would be wrapped around the tibia enclosingthe non-union in a “repair burrito.” The musculature and other softtissues would then envelope the repair site.

EXAMPLE 3 Preparation of Lyophilized Cubes

The putty prepared as described above is pressed into a Delrin mold,using a stainless steel laboratory spatula, or any other suitableutensil, or by hand, to create cubes, one centimeter on edge. The moldand putty is frozen on a dry ice slab, or any suitably chilled surfaceor freezer shelf or with liquid nitrogen, and placed, still frozen, intoa lyophilization flask. The putty is then subjected to a vacuum of 125mTorr for forty-eight hours while warming the lyophilization chamber toroom temperature, approximately 25° C. The lyophilized cubes can besterilized in a steam autoclave, as described above, prior to use. Thelyophilized cubes are dry in appearance but flexible and readily soak upblood and mix easily with bone marrow aspirate. The lyophilized cubescould be mixed with autograft bone harvested by conventional techniquesfrom areas such as the iliac crest and serve to expand the useful volumeof bone graft material available to the orthopedic surgeon.

When cancellous autograft bone is harvested from the iliac crest, acortical bone window is cut from the top of the ilium and cancellousbone is harvested from the space between the inner and outer corticalbone tables. Lyophilized cubes (or cylinders) are easily placed into thevoid created by the removal of the cancellous bone graft (FIG. 3). Thelyophilized cubes would facilitate the re-growth of host bone.

Lyophilized cubes or short lyophilized cylinders could be loaded intothe hollow central portion of a structural allograft device such as thefibular ring allograft device shown in FIG. 6, or machined allograftdowels, before insertion of the structural device into the preparedinter-vertebral body space.

The lyophilized putty, no matter what shape, is a firm but pliablemedical device that will retain its shape without a containment deviceas required with putty. Because the device is solid, it is easy tolocate or position in-vivo and, in the moist environment of the body, itwill hold its shape well and for an extended period of time. Because thelyophilized putty is porous, it adsorbs blood and other beneficial cellcontaining body fluids, such as bone marrow aspirate, contributing toits superior bone repair efficacy in comparison to the analogous putty.In addition these lyophilized putty devices are easier to terminallysteam sterilize than the analogous putty because there is virtually nomoisture present to boil and “blow-out” of the containment device(syringe). The glycerin or other fluid material that is present in theformulation lends pliability but has a low vapor pressure.

NaCMC is a key component of the hydrogel utilized in making thelyophilized putty. It is stable to the relatively high pH of theproduct. NaCMC is stable to steam sterilization and doesn't interferewith the biological action of the product. Other polysaccharidehydrogels such as hydroxyethyl cellulose (HEC), hydroxypropylmethylcellulose (HPC), methylcellulose (MC), and ethylcellulose (EC) maybe suitable substitutes for NaCMC. Some hydrogel materials, such ashyaluronic acid and chitosan, are not satisfactory because steamsterilization will cause these materials to degrade, losing viscosityand the ability to suspend particles.

Having described the present invention, it will be understood by thoseskilled in the art that many changes in construction and widelydiffering embodiments and applications of the invention will suggestthemselves without departing from the scope of the present invention.

1. A method for preparing a pliable medical device useful for repairingbone damage and promoting bone formation in mammals, the methodcomprising the steps of: (a) preparing a quantity of a hydrogelmaterial; (b) mixing said hydrogel material with a quantity of anosteoconductive component, forming a putty; and (c) lyophilizing saidputty, forming the pliable medical device.
 2. The method according toclaim 1 wherein step (a) further comprises the steps of: (a1) mixing aquantity of sodium carboxymethylcellulose with a quantity of glycerin;(a2) mixing, under a partial vacuum, said sodium carboxymethylcelluloseand said glycerin with a quantity of sterile water; (a3) increasing saidpartial vacuum while continuing mixing said sodiumcarboxymethylcellulose, said glycerin, and said sterile water; (a4)releasing said partial vacuum and ceasing said mixing; and (a5) allowingsaid sodium carboxymethylcellulose, said glycerin, and said sterilewater to hydrate at room temperature to form said hydrogel material. 3.The method according to claim 2 wherein in step (a1) instead of saidglycerin, mixing at least a one of a polyethylene glycol, an N-methylpyrrolidone, and a triacetin with said sodium carboxymethylcellulose. 4.The method according to claim 2 wherein in step (a1) instead of saidsodium carboxymethylcellulose, mixing at least a one of a hydroxyethylcellulose, a hydroxypropyl methylcellulose, a methylcellulose, and anethylcellulose with said glycerin.
 5. The method according to claim 2wherein in step (a1) instead of said sodium carboxymethylcellulose andsaid glycerin, mixing at least a one of a hydroxyethyl cellulose, ahydroxypropyl methylcellulose, a methylcellulose, and an ethylcellulosewith at least a one of a polyethylene glycol, an N-methyl pyrrolidone,and a triacetin.
 6. The method according to claim 1 wherein step (b)further comprises the step of: (b1) coating said osteoconductivecomponent with a biologically active peptide prior to said mixing step.7. The method according to claim 6 further comprising the step of: (b2)performing a final mixing of said hydrogel material and saidosteoconductive component that has been coated with said biologicallyactive peptide under a partial vacuum.
 8. The method according to claim6 wherein said biologically active peptide is a one of a P-15 peptidefragment, a chrysalin peptide fragment, an alpha1(I)-CB3 fragment, anRGD peptide containing fragment, a PTH fragment, and a cytomodulinprotein.
 9. The method according to claim 1 further comprising the stepof: (d) sterilizing the pliable medical device.
 10. The method accordingto claim 9 wherein step (d) further comprises the steps of: (d1) placingthe pliable medical device in a sealed but breathable microbial barrierpouch; (d2) placing said microbial barrier pouch containing the pliablemedical device into a steam autoclave; (d3) increasing a firsttemperature in said steam autoclave to a second temperature over a firstperiod of time; (d4) maintaining said second temperature in said steamautoclave over a second period of time; and (d5) cooling said secondtemperature down to a room temperature over a third period of time. 11.The method according to claim 9 further comprising the step of: (e)applying the pliable medical device to an osteogenic site.
 12. Themethod according to claim 11 wherein step (e) further comprises thesteps of: (e1) positioning a first end of the pliable medical device toa first osteogenic site; and (e2) positioning a second end of thepliable medical device to a second osteogenic site; wherein the pliablemedical device promotes bone formation beginning at said first andsecond ends of the pliable medical device, and meeting in the middle ofthe pliable medical device to form a new bone structure between saidfirst and second osteogenic sites.
 13. The method according to claim 12wherein said first osteogenic site is a portion of a first vertebra, andsaid second osteogenic site is a portion of a second vertebra.
 14. Themethod according to claim 11 wherein step (e) further comprises thesteps of: (e1) loading an open space of a non-union area between twofracture ends of a bone with autograft bone; and (e2) wrapping a sheetof said pliable medical device around said non-union area.
 15. Themethod according to claim 1 wherein said osteoconductive component iscomprised of particles having diameters between 250 microns to 425microns.
 16. The method according to claim 1 wherein saidosteoconductive component is comprised of particles having diametersbetween 50 microns to 2,000 microns.
 17. The method according to claim 1wherein step (c) further comprises the steps of: (c1) extruding at leastone cylinder of said putty onto a chilled surface that is at a firsttemperature below freezing; (c2) placing said at least one cylinder ofsaid putty onto a shelf of a lyophilization vessel; (c3) cooling said atleast one cylinder of said putty in said lyophilization vessel to asecond temperature colder than said first temperature; (c4) applying apartial vacuum to said lyophilization vessel; (c5) allowing saidlyophilization vessel to warm to room temperature or heated somewhatover a period of time; and (c6) removing at least one cylinder of thepliable medical device from said lyophilization vessel.
 18. The methodaccording to claim 1 wherein step (c) further comprises the steps of:(c1) injecting said putty into a sheet-like mold having a releasable topplate; (c2) placing said sheet-like mold containing said putty into afreezing unit; (c3) cooling said sheet-like mold containing said puttyin said freezing unit to a first temperature below freezing; (c4)loosening said releasable top plate of said sheet-like mold; (c5)placing said sheet-like mold containing said putty into a lyophilizationchamber; (c6) applying a partial vacuum to said lyophilization chamber;(c7) allowing said lyophilization chamber to warm to room temperature orheated somewhat over a period of time; and (c8) removing a flexiblesheet of the pliable medical device from said sheet-like mold.
 19. Themethod according to claim 1 wherein step (c) further comprises the stepsof: (c1) pressing said putty into a mold; (c2) creating a plurality ofcubes of said putty; (c3) placing said mold containing said plurality ofcubes of said putty onto a chilled surface until frozen; (c4) placing,while still frozen, said mold containing said plurality of cubes of saidputty into a lyophilization flask; (c5) applying a partial vacuum tosaid lyophilization flask; (c6) allowing said lyophilization flask towarm to room temperature or heated somewhat over a period of time; and(c8) removing a plurality of cubes of the pliable medical device fromsaid mold.
 20. The method according to claim 1 wherein step (c) furthercomprises forming said putty into the form of at least a one of acylinder, a cube, a sheet, a star, a toroid, a pyramid, a sphere, and anirregular shape prior to said lyophilization step.
 21. A composition ofmatter suitable for repairing bone damage and promoting bone formationin mammals comprising: a quantity of a hydrogel material; and a quantityof an osteoconductive component; wherein said hydrogel material and saidosteoconductive component are mixed to form a putty, and further whereinsaid putty is lyophilized to form a pliable medical device suitable forrepairing bone damage and promoting bone formation.
 22. The compositionof matter according to claim 21 wherein said hydrogel material furthercomprises: a quantity of sodium carboxymethylcellulose mixed with aquantity of glycerin, and further mixed, under a partial vacuum, with aquantity of sterile water; wherein after said mixing said sodiumcarboxymethylcellulose, said glycerin, and said sterile water is allowedto hydrate at room temperature.
 23. The composition of matter accordingto claim 22 wherein instead of said glycerin, at least a one of apolyethylene glycol, an N-methyl pyrrolidone and a triacetin is mixedwith said sodium carboxymethylcellulose.
 24. The composition of matteraccording to claim 22 wherein instead of said sodiumcarboxymethylcellulose, at least a one of a hydroxyethyl cellulose, ahydroxypropyl methylcellulose, a methylcellulose, and an ethylcelluloseis mixed with said glycerin.
 25. The composition of matter according toclaim 22 wherein instead of said sodium carboxymethylcellulose, at leasta one of a hydroxyethyl cellulose, a hydroxypropyl methylcellulose, amethylcellulose, and an ethylcellulose is mixed with at least a one of apolyethylene glycol, an N-methyl pyrrolidone, and a triacetin instead ofsaid glycerin.
 26. The composition of matter according to claim 21wherein said osteoconductive component is coated with a biologicallyactive peptide prior to said mixing.
 27. The composition of matteraccording to claim 26 wherein said hydrogel material and saidosteoconductive component that has been coated with said biologicallyactive peptide are finally mixed under a partial vacuum.
 28. Thecomposition of matter according to claim 26 wherein said biologicallyactive peptide is a one of a P-15 peptide fragment, a chrysalin peptidefragment, an alpha1(I)-CB3 fragment, an RGD peptide containing fragment,a PTH fragment, and a cytomodulin protein.
 29. The composition of matteraccording to claim 21 wherein said pliable medical device may besterilized before use.
 30. The composition of matter according to claim29 wherein said sterilization is performed in a steam autoclave.
 31. Thecomposition of matter according to claim 21 wherein said pliable medicaldevice is applied to an osteogenic site.
 32. The composition of matteraccording to claim 31 wherein a first end of said pliable medical deviceis positioned at a first osteogenic site, and a second end of saidpliable medical device is positioned at a second osteogenic site;wherein said pliable medical device promotes bone formation beginning atsaid first and second ends of said pliable medical device, and meetingin the middle of said pliable medical device to form a new bonestructure between said first and second osteogenic sites.
 33. Thecomposition of matter according to claim 32 wherein said firstosteogenic site is a portion of a first vertebra, and said secondosteogenic site is a portion of a second vertebra.
 34. The compositionof matter according to claim 31 wherein said osteogenic site is anon-union area between two fracture ends of a bone with autograft boneloaded in an open space of said non-union area, and further wherein asheet of said pliable medical device is wrapped around said non-unionarea.
 35. The composition of matter according to claim 21 wherein saidosteoconductive component is comprised of particles having diametersbetween 250 microns to 425 microns.
 36. The composition of matteraccording to claim 21 wherein said osteoconductive component iscomprised of particles having diameters between 50 microns to 2,000microns.
 37. The composition of matter according to claim 21 whereinsaid putty is formed into the form of at least a one of a cylinder, acube, a sheet, a star, a toroid, a pyramid, a sphere, and an irregularshape prior to lyophilization.
 38. A pliable medical device suitable forrepairing bone damage and promoting bone formation in mammals, made bythe process of: preparing a quantity of a hydrogel material; mixing saidhydrogel material with a quantity of an osteoconductive component,forming a putty; and lyophilizing said putty, forming the pliablemedical device.
 39. The pliable medical device according to claim 38wherein the process step of preparing said hydrogel material furthercomprises: mixing a quantity of sodium carboxymethylcellulose with aquantity of glycerin; mixing, under a partial vacuum, said sodiumcarboxymethylcellulose and said glycerin with a quantity of sterilewater; increasing said partial vacuum and continue mixing said sodiumcarboxymethylcellulose, said glycerin, and said sterile water; releasingsaid partial vacuum and ceasing said mixing; and allowing said sodiumcarboxymethylcellulose, said glycerin, and said sterile water to hydrateat room temperature to form said hydrogel material.
 40. The pliablemedical device according to claim 39 wherein the process furthercomprises the step of: mixing instead of said glycerin at least a one ofa polyethylene glycol, an N-methyl pyrrolidone, and a triacetin withsaid sodium carboxymethylcellulose.
 41. The pliable medical deviceaccording to claim 39 wherein the process further comprises the step of:mixing instead of said sodium carboxymethylcellulose at least a one of ahydroxyethyl cellulose, a hydroxypropyl methylcellulose, amethylcellulose, and an ethylcellulose with said glycerin.
 42. Thepliable medical device according to claim 39 wherein the process furthercomprises the step of: mixing instead of said sodiumcarboxymethylcellulose and said glycerin at least a one of ahydroxyethyl cellulose, a hydroxypropyl methylcellulose, amethylcellulose, and an ethylcellulose with at least a one of apolyethylene glycol, an N-methyl pyrrolidone, and a triacetin.
 43. Thepliable medical device according to claim 38 wherein said processfurther comprises the step of: coating said osteoconductive componentwith a biologically active peptide prior to said mixing step.
 44. Thepliable medical device according to claim 43 wherein the process furthercomprises the step of: performing a final mixing of said hydrogelmaterial and said osteoconductive component that has been coated withsaid biologically active peptide under a partial vacuum.
 45. The pliablemedical device according to claim 43 wherein said biologically activepeptide is a one of a P-15 peptide fragment, a chrysalin peptidefragment, an alpha1(I)-CB3 fragment, an RGD peptide containing fragment,a PTH fragment, and a cytomodulin protein.
 46. The pliable medicaldevice according to claim 38 wherein said process further comprises thestep of: sterilizing the pliable medical device.
 47. The pliable medicaldevice according to claim 46 wherein the process sterilizing stepfurther comprises the steps of: placing the pliable medical device in asealed but breathable microbial barrier pouch; placing said microbialbarrier pouch containing the pliable medical device into a steamautoclave; increasing a first temperature in said steam autoclave to asecond temperature over a first period of time; maintaining said secondtemperature in said steam autoclave over a second period of time; andcooling said second temperature down to a room temperature over a thirdperiod of time.
 48. The pliable medical device according to claim 46wherein the process further comprises the step of: applying the pliablemedical device to an osteogenic site.
 49. The pliable medical deviceaccording to claim 48 wherein the process of applying step furthercomprises the steps of: positioning a first end of the pliable medicaldevice to a first osteogenic site; and positioning a second end of thepliable medical device to a second osteogenic site; wherein the pliablemedical device promotes bone formation beginning at said first andsecond ends of the pliable medical device, and meeting in the middle ofthe pliable medical device to form a new bone structure between saidfirst and second osteogenic sites.
 50. The pliable medical deviceaccording to claim 49 wherein said first osteogenic site is a portion ofa first vertebra, and said second osteogenic site is a portion of asecond vertebra.
 51. The pliable medical device according to claim 48wherein the process further comprises the steps of loading an open spaceof a non-union area between two fracture ends of a bone with autograftbone; and wrapping a sheet of said pliable medical device around saidnon-union area.
 52. The pliable medical device according to claim 38wherein said osteoconductive component is comprised of particles havingdiameters between 250 microns to 425 microns.
 53. The pliable medicaldevice according to claim 38 wherein said osteoconductive component iscomprised of particles having diameters between 50 microns to 2,000microns.
 54. The pliable medical device according to claim 38 whereinthe process step of lyophilizing said putty further comprises the stepsof: extruding at least one cylinder of said putty onto a chilled surfacethat is at a first temperature below freezing; placing said at least onecylinder of said putty onto a shelf of a lyophilization vessel; coolingsaid at least one cylinder of said putty in said lyophilization vesselto a second temperature colder than said first temperature; applying apartial vacuum to said lyophilization vessel; allowing saidlyophilization vessel to warm to room temperature or heated somewhatover a period of time; and removing at least one cylinder of the pliablemedical device from said lyophilization vessel.
 55. The pliable medicaldevice according to claim 38 wherein the process step of lyophilizingsaid putty further comprises the steps of: injecting said putty into asheet-like mold having a releasable top plate; placing said sheet-likemold containing said putty into a freezing unit; cooling said sheet-likemold containing said putty in said freezing unit to a first temperaturebelow freezing; loosening said releasable top plate of said sheet-likemold; placing said sheet-like mold containing said putty into alyophilization chamber; applying a partial vacuum to said lyophilizationchamber; allowing said lyophilization chamber to warm to roomtemperature or heated somewhat over a period of time; and removing aflexible sheet of the pliable medical device from said sheet-like mold.56. The pliable medical device according to claim 38 wherein the processstep of lyophilizing said putty further comprises the steps of: pressingsaid putty into a mold; creating a plurality of cubes of said putty;placing said mold containing said plurality of cubes of said putty ontoa chilled surface until frozen; placing, while still frozen, said moldcontaining said plurality of cubes of said putty into a lyophilizationflask; applying a partial vacuum to said lyophilization flask; allowingsaid lyophilization flask to warm to room temperature or heated somewhatover a period of time; and removing a plurality of cubes of the pliablemedical device from said mold.
 57. The pliable medical device accordingto claim 38 wherein the process step of lyophilizing said putty furthercomprises forming said putty into the form of at least a one of acylinder, a cube, a sheet, a star, a toroid, a pyramid, a sphere, and anirregular shape prior to lyophilization.